The Neuro Team
Peter McPherson, PhD
Dr. McPherson's laboratory has previously used subcellular proteomics (subcellular fractionation coupled to high throughput mass spectrometry) to identify the full complement of proteins that define CCVs from adult brain, developing brain and non-neuronal tissues. A significant number of the proteins identified were uncharacterized open-reading frames. Dr. McPherson's laboratory has characterized the function of a number of these novel proteins, although a significant number remain unstudied. One recently identified protein contains a module called a DENN domain. Dr. McPherson and his colleagues have demonstrated that the DENN domain functions enzymatically as a guanine-nucleotide exchange factor for the small GTPase Rab35. There are 16 DENN domain proteins in the human genome. An important area of study involves the relationship of these proteins to the ~60 Rabs that function in membrane traffic.
A number of proteins identified in the McPherson laboratory have been linked to neurological diseases, including schizophrenia, Huntington's Disease, hereditary spastic paraplegias (ALS-like), and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Indeed, dysregulation of membrane trafficking is emerging as a central theme in neurodegenerative diseases. Understanding the cell biological basis of neurological disease is a new focus of the laboratory.